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Drug Interactions between Glyceryl T and regadenoson

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

theophylline regadenoson

Applies to: Glyceryl T (guaifenesin / theophylline) and regadenoson

ADJUST DOSING INTERVAL: Methylxanthines (e.g., caffeine, theophylline) are nonspecific, competitive antagonists of adenosine receptors. As such, they may interfere with the pharmacologic effects of adenosine and other adenosine receptor agonists such as dipyridamole and regadenoson. There have been case reports of patients receiving theophylline who required higher than normal dosages of adenosine for the treatment of paroxysmal supraventricular tachycardia. In studies of healthy volunteers, caffeine and theophylline have been shown to reduce the cardiovascular response to adenosine infusions (i.e., heart rate increases, vasodilation, blood pressure changes), and theophylline has also been shown to attenuate adenosine-induced respiratory effects and chest pain/discomfort. Similarly, caffeine has been found to reduce the hemodynamic response to dipyridamole, and both caffeine and theophylline have been reported to cause false-negative results in myocardial scintigraphy tests using dipyridamole. In a placebo-controlled study that assessed the effects of oral caffeine on regadenoson-induced increase in coronary flow reserve (CFR), healthy subjects who took caffeine 200 mg orally two hours prior to regadenoson administration exhibited a median CFR that was 92% that of subjects who took placebo. The study was done using positron emission tomography with radiolabeled water.

MANAGEMENT: Clinicians should be aware that adenosine and other adenosine receptor agonists may be less effective in the presence of methylxanthines. Methylxanthines including caffeine should be withheld for 12 to 24 hours (or five half-lives) prior to administration of adenosine receptor agonists for myocardial perfusion imaging. However, parenteral aminophylline should be readily available for treating severe or persistent adverse reactions to adenosine receptor agonists such as bronchospasm or chest pain.

References

  1. Conti CR "Adenosine: clinical pharmacology and applications." Clin Cardiol 14 (1991): 91-3
  2. Smits P, Aengevaeren WR, Corstens FH, Thien T "Caffeine reduces dipyridamole-induced myocardial ischemia." J Nucl Med 30 (1989): 1723-6
  3. Smits P, Schouten J, Thien T "Respiratory stimulant effects of adenosine in man after caffeine and enprofylline." Br J Clin Pharmacol 24 (1987): 816-9
  4. Minton NA, Henry JA "Pharmacodynamic interactions between infused adenosine and oral theophylline." Hum Exp Toxicol 10 (1991): 411-8
  5. "Product Information. Persantine (dipyridamole)." Boehringer-Ingelheim PROD (2002):
  6. "Product Information. Adenocard (adenosine)." Fujisawa PROD (2001):
  7. Ranhosky A, Kempthorne-Rawson J, the Intravenous Dipyridamole Thallium Imaging Study Group "The safety of intravenous dipyridamole thallium myocardial perfusion imaging." Circulation 81 (1990): 1205-9
  8. "Product Information. Adenoscan (adenosine)." Fujisawa (2001):
  9. "Product Information. Lexiscan (regadenoson)." Astellas Pharma US, Inc (2008):
View all 9 references

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Drug and food interactions

Moderate

theophylline food

Applies to: Glyceryl T (guaifenesin / theophylline)

GENERALLY AVOID: Coadministration with caffeine may increase the serum concentrations of theophylline. The proposed mechanism involves competitive inhibition of theophylline metabolism via CYP450 1A2, as well as metabolic conversion of caffeine to theophylline in vivo and saturation of theophylline metabolism at higher serum concentrations. In six healthy male volunteers (all smokers), serum concentrations of theophylline (administered as aminophylline 400 mg single oral dose) were significantly higher following consumption of caffeine (2 to 7 cups of instant coffee over 24 hours, equivalent to approximately 120 to 630 mg of caffeine) than after caffeine deprivation for 48 hours. Caffeine consumption also increased the apparent elimination half-life of theophylline by an average of 32% and reduced its total body clearance by 23%. In another study, steady-state concentration and area under the concentration-time curve of theophylline (1200 mg intravenously over 24 hours) increased by 23% and 40%, respectively, in eight healthy volunteers following administration of caffeine (300 mg orally three times a day).

MANAGEMENT: Given the narrow therapeutic index of theophylline, patients should limit or avoid significant fluctuations in their intake of pharmacologic as well as dietary caffeine.

ADJUST DOSING INTERVAL: Administration of theophylline with continuous enteral nutrition may reduce the serum levels or the rate of absorption of theophylline. The mechanism has not been reported. In one case, theophylline levels decreased by 53% in a patient receiving continuous nasogastric tube feedings and occurred with both theophylline tablet and liquid formulations, but not with intravenous aminophylline.

MANAGEMENT: When administered to patients receiving continuous enteral nutrition , some experts recommend that the tube feeding should be interrupted for at least 1 hour before and 1 hour after the dose of theophylline is given; rapid-release formulations are preferable, and theophylline levels should be monitored.

References

  1. Jonkman JH, Sollie FA, Sauter R, Steinijans VW "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther 49 (1991): 248-55
  2. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol 44 (1993): 295-8
  3. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm 66 (2009): 1438-67

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Moderate

regadenoson food

Applies to: regadenoson

ADJUST DOSING INTERVAL: Caffeine and other xanthine derivatives are nonspecific, competitive antagonists of adenosine receptors. As such, they may interfere with the vasodilating effect of regadenoson, an adenosine receptor agonist. In a placebo-controlled study that assessed the effects of oral caffeine on regadenoson-induced increase in coronary flow reserve (CFR), healthy subjects who took caffeine 200 mg orally two hours prior to regadenoson administration exhibited a median CFR that was 92% that of subjects who took placebo. The study was done using positron emission tomography with radiolabeled water.

MANAGEMENT: Patients should avoid consumption of caffeine-containing products for at least 12 hours prior to administration of regadenoson for myocardial perfusion imaging.

References

  1. "Product Information. Lexiscan (regadenoson)." Astellas Pharma US, Inc (2008):

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Moderate

theophylline food

Applies to: Glyceryl T (guaifenesin / theophylline)

GENERALLY AVOID: Coadministration with caffeine may increase the serum concentrations of theophylline. The proposed mechanism involves competitive inhibition of theophylline metabolism via CYP450 1A2, as well as metabolic conversion of caffeine to theophylline in vivo and saturation of theophylline metabolism at higher serum concentrations. In six healthy male volunteers (all smokers), serum concentrations of theophylline (administered as aminophylline 400 mg single oral dose) were significantly higher following consumption of caffeine (2 to 7 cups of instant coffee over 24 hours, equivalent to approximately 120 to 630 mg of caffeine) than after caffeine deprivation for 48 hours. Caffeine consumption also increased the apparent elimination half-life of theophylline by an average of 32% and reduced its total body clearance by 23%. In another study, steady-state concentration and area under the concentration-time curve of theophylline (1200 mg intravenously over 24 hours) increased by 23% and 40%, respectively, in eight healthy volunteers following administration of caffeine (300 mg orally three times a day).

MANAGEMENT: Given the narrow therapeutic index of theophylline, patients should limit or avoid significant fluctuations in their intake of pharmacologic as well as dietary caffeine.

References

  1. Jonkman JH, Sollie FA, Sauter R, Steinijans VW "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther 49 (1991): 248-55
  2. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol 44 (1993): 295-8

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

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